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Among them, macrophage membrane\u2010coated nanoparticles hold particular appeal due to their versatility in drug delivery and biological neutralization applications. This study employs a genetic engineering approach to enhance their in vivo residence times, aiming to further improve their performance. Specifically, macrophages are engineered to express proline\u2010alanine\u2010serine (PAS) peptide chains, which provide additional protection against opsonization and phagocytosis. The resulting modified nanoparticles demonstrate prolonged residence times when administered intravenously or introduced intratracheally, surpassing those coated with the wild\u2010type membrane. The longer residence times also contribute to enhanced nanoparticle efficacy in inhibiting inflammatory cytokines in mouse models of lipopolysaccharide\u2010induced lung injury and sublethal endotoxemia, respectively. This study underscores the effectiveness of genetic modification in extending the in vivo residence times of macrophage membrane\u2010coated nanoparticles. This approach can be readily extended to modify other cell membrane\u2010coated nanoparticles toward more favorable biomedical applications.<\/jats:p>","DOI":"10.1002\/smll.202305551","type":"journal-article","created":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T22:25:04Z","timestamp":1693175104000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Extending the In Vivo Residence Time of Macrophage Membrane\u2010Coated Nanoparticles through Genetic Modification"],"prefix":"10.1002","volume":"19","author":[{"given":"Yaou","family":"Duan","sequence":"first","affiliation":[{"name":"Department of NanoEngineering Chemical Engineering Program and Moores Cancer Center University of California San Diego  La Jolla San Diego CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of NanoEngineering Chemical 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